The erythrocyte membrane is generally considered as consisting of a bimolecular layer of phospholipid, with various protein molecules penetrating the bilayer and other protein molecules attached to its surfaces. The membrane inner surface is lined by a network of protein molecules, consisting largely of the high molecular weight protein, spectrin. The several membrane phospholipids are asymmetrically distributed between the inner and outer shells of the bilayer. Measurements on age (density) fractionated erythrocytes showed that the phospholipid asymmetry does not change over the cell lifetime, thus suggesting a functional role for the existent asymmetric distribution. To determine whether interactions with membrane phospholipids contributes to the stability of the spectrin network, a study was made of the effect of enzymatic hydrolysis of membrane phospholipid on the dissociation of spectrin from the membrane. Hydrolysis of 50% of the phospholipids of the outer shell of the bilayer had no effect on the dissociation rates, while hydrolysis of inner bilayer shell phospholipids increased these rates, by up to twofold for hydrolysis of all inner shell phospholipid. Work is in progress to determine whether this increase is a direct effect of disruption of spectrin-phospholipid interactions.